Aggressiveness in Italian Children with ADHD: MAOA Gene Polymorphism Involvement

Diseases Pub Date : 2024-03-31 DOI:10.3390/diseases12040070
Ludovico Neri, B. Marziani, P. Sebastiani, Tiziana Del Beato, A. Colanardi, Maria Pia Legge, A. Aureli
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Abstract

ADHD is a neurodevelopmental disorder that children and adults can develop. A complex interplay of genetic and environmental factors may underlie interindividual variability in ADHD and potentially related aggressive behavior. Using high-resolution molecular biology techniques, we investigated the impact of some MAOA and SLC6A4 variations on ADHD and aggressive behavior in a group of 80 Italian children with ADHD and in 80 healthy controls. We found that homozygous genotypes of MAOA rs6323 and rs1137070 were associated with an increased risk of ADHD (p = 0.02 and p = 0.03, respectively), whereas the heterozygous genotypes (GT of rs6323 and CT of rs1137030) (p = 0.0002 and p = 0.0006) were strongly linked to a lower risk of developing this disorder. In patients with aggressive behavior, we highlighted only a weak negative association of both MAOA polymorphisms (heterozygous genotypes) with aggressiveness, suggesting that these genotypes may be protective towards specific changes in behavior (p = 0.05). Interestingly, an increase in the GG genotype of rs6323 (p = 0.01) and a decrease in GT genotype (p = 0.0005) was also found in patients without aggressive behavior compared to controls. Regarding 5HTT gene genotyping, no allele and genotype differences have been detected among patients and controls. Our work shows that defining a genetic profile of ADHD may help in the early detection of patients who are more vulnerable to ADHD and/or antisocial and aggressive behavior and to design precision-targeted therapies.
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意大利多动症儿童的攻击性:MAOA 基因多态性的影响
多动症是一种神经发育障碍,儿童和成年人都可能患上。遗传和环境因素的复杂相互作用可能是多动症个体间差异和可能相关的攻击行为的基础。我们利用高分辨率分子生物学技术,在一组 80 名患有多动症的意大利儿童和 80 名健康对照者中调查了 MAOA 和 SLC6A4 变异对多动症和攻击行为的影响。我们发现,MAOA rs6323 和 rs1137070 的同源基因型与多动症风险增加有关(分别为 p = 0.02 和 p = 0.03),而杂合基因型(rs6323 的 GT 型和 rs1137030 的 CT 型)(p = 0.0002 和 p = 0.0006)则与患这种疾病的风险降低密切相关。在有攻击性行为的患者中,我们发现 MAOA 两种多态性(杂合子基因型)与攻击性只有微弱的负相关,这表明这些基因型可能对特定的行为变化具有保护作用(p = 0.05)。有趣的是,与对照组相比,在无攻击性行为的患者中还发现 rs6323 的 GG 基因型增加(p = 0.01),GT 基因型减少(p = 0.0005)。在 5HTT 基因基因分型方面,未发现患者和对照组之间存在等位基因和基因型差异。我们的研究结果表明,确定多动症的遗传特征有助于及早发现更易患多动症和/或反社会及攻击行为的患者,并设计出精准的靶向疗法。
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